Vortioxetine hydrobromide is indicated for the treatment of major depressive disorder (MDD). It is a serotonin (5-HT) reuptake inhibitor, which is considered as its mechanism of action for the treatment of MDD. It is available in the market as brand name of BRINTELLIX which contains the beta (β) polymorph of Vortioxetine hydrobromide, an antidepressant.
Vortioxetine was first described in U.S. Pat. No. 7,144,884. It describes manufacturing process of Vortioxetine. It involves resin base support to prepare Vortioxetine. Process is as describe in below scheme.

WO2007144005A1 describes manufacturing process for the preparation of Vortioxetine. The first step of it involves cross coupling reaction between 2,4-dimethylthiophenol and 2-bromoiodobenzene using Pd catalysis in presence of phosphine ligand and base which furnish I-(2-Bromo-phenylsulfanyl)-2,4-dimethylbenzene which was reacted with unprotected piperazine or protected to furnish respectively 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-piperazine or (4-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-BOC-piperazine). Protected BOC group was removed by HCl to produce Vortioxetine. This patent also describes one pot process for the synthesis of Vortioxetine.
WO2013102573A1 describes one pot process for the preparation of Vortioxetine. It involves a coupling reaction between 1-iodo-2,4-dimethylbenzene, 2-bromo thiophenol and piperazine in presence of Pd catalyst, phosphine ligand and base to furnish 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-piperazine.
Furthermore, WO2007144005 discloses different polymorph of Vortioxetine base and its salt. They mainly focused on crystalline base, alpha form of hydrobromide salt, beta form of hydrobromide salt, gamma form of hydrobromide salt, hemi hydrate of hydrobromide salt, the mixture of the ethyl acetate solvate and the alpha form of the hydrobromide salt, hydrochloride salt, monohydrate of hydrochloride salt, mesylate salt, fumarate salt, maleate salt, meso-tartrate salt, L-(+)-tartrate salt, D-(−)-tartrate salt, sulphate salt, phosphate salt, nitrate salt of Vortioxetine.
WO2010121621A1 discloses AH1, MH1 & MH2 form of Vortioxetine-lactate and also discloses α, β, γ and MH form of Vortioxetine DL-lactate.
WO2010094285 discloses Vortioxetine HBr isopropanol solvate.
WO2014044721 discloses delta form of Vortioxetine HBr.
WO2014177491 discloses amorphous form of Vortioxetine hydrobromide with an adsorbent.
The acceptable amount of solvents in an active pharmaceutical ingredient is strictly regulated e.g. by the ICH guideline for residual solvents. Solvates of Vortioxetine hydrobromide such as e.g. the ethyl acetate solvate of WO 2007/144005 A1 and the isopropanol solvate of WO 2010/094285 A1 are no suitable crystalline forms for the preparation of a medicament as they clearly exceed the recommended solvent amount for class 3 solvents. In summary, solvates of Vortioxetine hydrobromide know in the art are no suitable forms for the preparation of a medicament due to the strict limits for residual solvents in an active pharmaceutical ingredient.
Polymorphism is defined as “the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC) and Infrared spectrometry (IR).
A polymorphic form may be referred to herein as being characterized by graphical data “as shown in” a Figure. Such data include, for example, powder X-ray diffractograms. In any event, the skilled person will understand that such graphical representations of data may be subject to small variations, e.g., in peak relative intensities and peak positions due to factors such as variations in instrument response and variations in sample concentration and purity, which factors are well known to the skilled person.
The technical problem underlying the present invention is to circumvent the drawbacks of the known crystalline forms of Vortioxetine hydrobromide disclosed in the state of the art such as toxicity issues of solvates, stability issues due to water uptake, bioavailability issues due to limited solubility and preparation issues due to similar crystallization processes by providing novel polymorphic forms of Vortioxetine and its pharmaceutically acceptable salts which shows high solubility and is obtained in polymorphically pure form in an easy and reliable manner.